Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4.

ABSTRACT: The molecular mechanisms underlying the regulation of pluripotency by cellular metabolism in human embryonic stem cells (hESCs) are not fully understood. We found that high levels of glutamine metabolism are essential to prevent degradation of OCT4, a key transcription factor regulating hESC pluripotency. Glutamine withdrawal depletes the endogenous antioxidant glutathione (GSH), which results in the oxidation of OCT4 cysteine residues required for its DNA binding and enhanced OCT4 degradation. The emergence of the OCT4(lo) cell population following glutamine withdrawal did not result in greater propensity for cell death. Instead, glutamine withdrawal during vascular differentiation of hESCs generated cells with greater angiogenic capacity, thus indicating that modulating glutamine metabol

SUBMITTER: Marsboom G 

PROVIDER: S-EPMC4945388 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature